Abstract
Normal lung morphogenesis is dependent on chloride-driven fluid transport. The molecular identity of essential fetal lung chloride channel(s) has not been elucidated. CLC-2 is a chloride channel, which is expressed on the apical surface of the developing respiratory epithelium. CLC-2-like pH-dependent chloride secretion exists in fetal airway cells. We used a 14-day fetal rat lung submersion culture model to examine the role of CLC-2 in lung development. In this model, the excised fetal lung continues to grow, secrete fluid, and become progressively cystic in morphology (26). We inhibited CLC-2 expression in these explants, using antisense oligonucleotides, and found that lung cyst morphology was disrupted. In addition, transepithelial voltage (Vt) of lung explants transfected with antisense CLC-2 was inhibited with V t = -1.5 ± 0.2 mV (means + SE) compared with -3.7 ± 0. 3 mV (means + SE) for mock-transfected controls and -3.3 ± 0.3 mV (means + SE) for nonsense oligodeoxynucleotide-transfected controls. This suggests that CLC-2 is important for fetal lung fluid production and that it may play a role in normal lung morphogenesis.
Original language | English (US) |
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Pages (from-to) | L420-L426 |
Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
Volume | 286 |
Issue number | 2 30-2 |
DOIs | |
State | Published - Feb 2004 |
Externally published | Yes |
Keywords
- Chloride secretion
- Lung development
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology